Alcohol health disparities research shows that, despite higher prevalence rates of alcohol dependence for whites, blacks and Hispanics experience more adverse social and health effects from drinking and greater alcohol dependence severity. The scientific understanding for how ethnic alcohol disparities develop and are sustained has lagged behind their recognition. The long-term career goal for the candidate of this Mentored Research Scientist Development Award (K01) application, Karen G. Chartier, PhD, is to better understand the interrelationships between genetic, social, and macro-environment factors that affect alcohol consequences for ethnic minority groups. The objectives for this particular application are to test the relationship of alcohol metabolizing genes to phenotypes relevant to alcohol dependence for blacks and Hispanics, and to investigate gene-environment interactions for alcohol dependence severity. These objectives will be accomplished by examining three specific aims: 1) to evaluate the effect of alcohol metabolizing alleles on alcohol dependence symptoms and adverse reactions to drinking; 2) to test social factors as moderators of genetic susceptibility for alcohol dependence severity; and 3) to examine the effects of neighborhood social factors on alcohol dependence severity and genetic susceptibility. The proposed studies will utilize previously collected data from the Collaborative Study on the Genetics of Alcoholism (COGA) and publicly available data from the U.S. Census Bureau that describe neighborhood characteristics at the census tract level. Subjects will be black, Hispanic, and white adult COGA subjects, ages 18 years and older, including those affected and unaffected by alcoholism. This research is innovative because it: examines genetic factors in understudied black and Hispanic populations; investigates relationships for alcohol metabolizing genes to more narrowly defined alcohol symptoms; and tests the relationships between the social environment and genetic susceptibility for alcohol dependence severity. The candidate will conduct the proposed research under the mentorship of Raul Caetano, MD, PhD and a team of co-mentors to gain expertise in phenotypes for alcohol dependence, genetics research with ethnic minority groups, and methodologies for examining genetic and social factors. Training activities will include coursework and mentoring in genetics and advanced statistical applications, geocoding for spatial-based data, research ethics, and grantsmanship. Ultimately, this training will prepare the candidate to integrate genetic and social variables in alcohol studies and will facilitate her contribution to health disparities research. It is anticipaed that the proposed studies will lead to advances in alcohol genetics research and further efforts to explain the differences in alcohol severity for blacks, Hispanics, and whites. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because expanded scientific knowledge about the relationship of genes to more narrowly defined phenotypes of alcoholism is expected to advance the identification of useful phenotypic targets in black and Hispanic populations. The analysis of gene-environment interactions will improve the understanding of subgroups of blacks and Hispanics with greater or lesser risk for alcohol dependence severity, information important for developing targeted policy and intervention strategies. The proposed research and career training are relevant to the NIH/NIAAA's strategic goals aimed at reducing alcohol-related health disparities for ethnic minority groups.